Phrenic Nerve and Diaphragmatic Stimulation

ES options for the restoration of inspiratory muscle function in people with SCI include bilateral phrenic nerve pacing, bilateral diaphragmatic pacing and combined intercostal muscle stimulation with unilateral phrenic pacing (DiMarco et al. 2005a).

Intact phrenic nerves are required for successful stimulation. Phrenic nerve function is generally assessed through phrenic nerve conduction studies and fluoroscopic observation of diaphragmatic movement with PNS. People with injuries at C3, C4 and C5 may have compromised diaphragmatic function, but are unlikely to be candidates for pacing due to inadequate phrenic nerve function.

Bilateral PNS was first reported by Glenn and colleagues in the 1970s. The original surgery involved a thoracotomy and inpatient hospital stay to place the electrodes on the phrenic nerves in the neck or thorax. Potential risks included direct injury to the phrenic nerves during surgery. The original protocols applied intermittent high frequency stimulation to the diaphragms in an alternating pattern, but were revised to a continuous lower frequency stimulation to decrease diaphragmatic fatigue (Glenn et al. 1984; Elefteriades et al. 2002).

In recent years, the laparoscopic placement of intramuscular diaphragmatic electrodes has eliminated the need for more extensive thoracotomy surgery and associated hospital stays. The approach has also decreased the risk of phrenic nerve injury (DiMarco et al. 2005a). The electrodes are placed laparoscopically as a day surgery procedure with optimum placement of the electrodes being mapped to the phrenic nerve motor point (Onders el al. 2004).

Most patients with diaphragmatic pacemakers continue to have tracheostomies and mechanical ventilators as a back-up to their pacemakers. It is important to note that diaphragmatic pacemakers only improve inspiratory function and do not target expiratory functions such as coughing and clearing secretions. Given the small number of controlled trials and large number of pre-post trials, the full data extraction and scoring are only shown for the controlled trials with a briefer summary of the level 4 evidence.


Recent studies show higher success rates with long-term implantation (DiMarco et al. 2014; Hirschfeld et al. 2013); 77% of patients had stable threshold currents for an average of 6.3 yr. Hirschfeld et al. (2008) prospectively compared people receiving PNS and those receiving MV. Although they showed decreased rates of RI and increased social participation in the PNS group, they acknowledged that the MV group is not a comparable group as these participants were not usually candidates for PNS.

The prospective study by Hirschfeld et al. (2008) shows no difference in duration of life between the phrenic nerve paced group and mechanically ventilated group.

Hirschfeld et al. (2008) comment on decreased costs of care, improved quality of speech and higher rates of social participation in the phrenic nerve group. The increased rates of return to work and school may have been influenced by the lower ages seen in the phrenic nerve group. Prospective comparison studies looking at morbidity, mortality, QOL and costs related to phrenic and diaphragmatic pacing are lacking.

Several different devices for phrenic nerve pacing have been developed. Reported benefits to participants include improved sense of smell, mobility, quality of speech, comfort, QOL, and overall sense of well-being (Le Pimpec-Barthes et al. 2011; DiMarco et al. 2005b). Long-term partial or total independence from MV can be interpreted as a successful intervention with these devices.

Bilateral phrenic nerve pacing and bilateral diaphragmatic pacing can be used successfully for the ventilation of people with SCI (Kaufman et al. 2015; Baer et al. 1990; DiMarco et al. 2005a; Elefteriades et al. 2002; Onders et al. 2004). More recent studies have included larger sample sizes, including the study by Onders et al. (2018) (n = 92); Wijkstra et al. (2022) (n = 33); Monden et al. (2022) (n = 28); and Alshekhlee et al. (2008) (n = 26).

The diaphragm pacing system (DPS) is a successful strategy for managing respiration in patients with high SCI; between 73% and 77% of participants achieved 4-h of independent use of the DPS at 6 and 12 months of follow-up (Wijkstra et al. 2022). The use of a DPS requires a period of acclimation to achieve full effectiveness of the therapy, especially if the patient has been mechanically ventilated for a long period, due to increased levels of diaphragm atrophy and greater dependence on MV (Wijkstra et al. 2022). Some studies recommend early implantation of the DPS (Onders et al. 2018) and a gradually increased and individualized diaphragm conditioning period (Alshekhlee et al. 2008; DiMarco et al. 2005a; Onders et al. 2004; Tedde et al. 2012).

Unilateral phrenic pacing in combination with intercostals stimulation can be used successfully for the ventilation of people with SCI with only one intact phrenic nerve (DiMarco et al. 2005b). Several small studies (Krieger & Krieger 2000; Nandra et al. 2017; Verin et al. 2017) report successful reinnervation of the diaphragm in intercostal to phrenic nerve transfer in patients with SCI. Verin et al. (2017) showed no changes in nasoendoscopic findings, no swallowing disorders for food or liquid, no episode of laryngeal aspiration or bronchial penetration, or no noticeable change in voice were shown at 6 to 24 months of follow-up. However, this procedure was associated with diaphragm reinnervation, even if at 36 months none of the patients could restore their automatic ventilation (Verin et al. 2017). Dimarco et al. (1994) found that intercostal muscle pacing via upper thoracic ventral root stimulation alone has not succeeded in supporting ventilation for prolonged periods. There is at least one case report of the successful off label use of a spinal cord stimulator (rather than a purpose built phrenic nerve stimulator) being used to stimulate the phrenic nerves in people with SCI (Taira & Hori 2007).

Potential complications of phrenic pacing include wires breaking, wires or receivers becoming displaced, devices failing, aspiration of food during inspiration, shoulder or abdominal pain and infections (Baer et al. 1990; DiMarco et al. 2005a, 2005b). With the laparoscopic approach for DP, people may develop pneumothoraces or subcutaneous emphysema (DiMarco et al. 2005a).


There is level 3 evidence (from one case control study: Carter 1993) that suggests a higher survival rate in a phrenic nerve paced group compared to a mechanically ventilated group.

There is level 4 evidence (from 10 pre-post studies and two case series: see Table 18) that PNS can be used as a long-term alternative to MV for people with injuries at C2 or above.

There is level 4 evidence (Tedde et al. 2012; DiMarco et al. 2005a; Onders et al. 2004; Onders et al. 2018; Wijkstra et al. 2022) that diaphragmatic stimulation via laparoscopic placement of electrodes can be used as a long-term alternative to MV for people with high cervical SCI.

There is level 4 evidence (from one pre-post study and two case series: Alshekhlee et al. 2008, Onders et al. 2018; Wijkstra et al. 2022) and level 5 evidence (from one observational study: Monden et al. 2022) that DPS can help patients with cervical SCI to breathe without a mechanical ventilator.

There is level 4 evidence (from one study: DiMarco et al. 2005b) that unilateral phrenic stimulation, in combination with intercostals stimulation, can be used as an alternative to MV for people with a single intact phrenic nerve.

There is level 4 evidence (from one pre – post study: Nandra et al. 2017) that intercostal to phrenic nerve transfer was feasible and successful in reinnervating the diaphragm and limiting ventilator dependence in patients with SCI.

There is level 4 evidence (from one pre – post study: Verin et al. 2017) that the unilateral diaphragmatic reinnervation by the inferior laryngeal nerve is feasible and provides diaphragm reinnervation, but does not restore the automatic ventilation in ventilator-dependent patients with cervical SCI.

There is level 4 evidence (from one study: DiMarco et al. 1994) that intercostal muscle pacing via upper thoracic ventral root stimulation cannot be used as a long-term alternative to MV.